Journal of IiME Volume 2 Issue 1 www.investinme.org WHO GETS ME AND WHY - The role of impaired capillary blood flow in ME (continued) Such findings are in accord with the idea that ME is a dysfunctional state arising from inadequate rates of delivery of oxygen and nutrient substrates, rather than a condition associated with tissue pathology. That viewpoint is consistent also, with the improved wellbeing of patients who respond to agents which improve red cel deformability and thus increase capillary blood flow. TREATMENT OPTIONS The major factors in the development of the dysfunctional state manifested as the symptoms of ME are the presence of randomly distributed clusters of small capillaries and the effects of shape-changed, poorly deformable red cells on the rate of capillary blood flow. As it is not possible to influence capillary size, treatment should be aimed at improving red cell deformability, as remissions show that the red cell changes are reversible. 1. Acute ME. As reported at the Cambridge Symposium, a chance event led to an investigation iiv into the possible benefits of injections of vitamin B12 as hydroxocobalamin. A female patient reported that her general practitioner had given her an injection of hydroxocobalamin (Neo-Cytamen) and within 24 hours she felt much better. A blood sample was taken and revealed that her level of cup forms was reduced greatly. However, another patient failed to benefit from a similar injection and there was no change in her cup form value. The improved status of the responder was maintained with injections at about 10 day intervals. Through the co-operation of general practitioners it was found that 15 of 29 cases of ME responded to injections of hydroxocobalamin with symptom relief and reduced cup forms. However, there is no explanation of the mode of action of the B12 or why it was ineffective in 50% of cases. 2. Chronic ME. Some understanding of how the red cell changes in chronic ME might be relieved is based upon two early studies which investigated the effects of prostaglandins on red blood cells. Kury et al (26) used a spin-labelling technique to assess factors in red cells which influenced cell deformability. They reported that prostaglandin E1 (PGE1) increased red cell deformability, while the pro-inflammatory prostaglandin E2 (PGE2) had the opposite effect. By means of a filtration technique based upon standardised paper filters, Rasmussen et al (27) showed that PGE1 improved the filtration rate, while PGE2 had the opposite effect. Those observations were consistent with the findings of Kury et al, but in addition it was reported that catecholamines also reduced the rate of filtration. to explain why both emotional and physical stress are causal factors in the relapses of ME people. Although cis-linoleic acid is the basic precursor for Invest in ME (Charity Nr. 1114035) PGE1, it has to be elongated to gammalinolenic acid (GLA) in a reaction mediated by the enzyme delta-6desaturase. However it is known that in a number of situations the enzyme becomes dysfunctional, impairing the synthesis of GLA. For that reason it has been found useful to use plant sources of GLA. The most effective source is oil of evening primrose although it is unclear why it is responsible for higher production of PGE1 than other plant oils, even if their GLA content is higher. Manku et al (28) have reported that 2 grams daily of oil of evening primrose had no effect on the blood levels of PGE1, while 4 grams daily of the oil caused a significant increase in the concentration of PGE1 in the blood. So at least 4 grams daily of oil of evening primrose is needed to be effective. It needs to be emphasised that for unexplained reasons, not all individuals respond to that dose of evening primrose oil. The omega-3 fatty acids also have the ability to improve red cell deformability and may offer an alternative. The smallest omega-3 is the plant-derived alphalinolenic acid which requires a functional delta-6desaturase to elongate it in the synthesis of eicosapentaenoic acid. Because of the potential problems of delta-6-desaturase it is preferable to take omega-3 in the form of fish oil which is rich in eicosapentaenoic and docosohexanoic acids. Having demonstrated previously, by the use of a spinlabelling technique, that the lipid bilayer of the membranes of diabetic red cells were very viscous, (29) Kamada et al (30) reported that sardine oil taken orally, increased the fluidity of the lipid bilayer and increased the cell deformability. Although some ME people have responded to fish oil, I have not been able to identify which patients will respond to what oil. A lack of funding has prevented investigations into the performance of the oils by double-blinded randomised studies. However, on the result sheets concerning red cell shape analyses, in addition to the results, and a copy of the micrograph there is a suggestion that the effects of the changed red cells might be reduced by a daily intake of 4 grams of oil of evening primrose or 6 grams of fish oil. It is noted also, that if no benefit is perceived by 6 weeks, then another treatment should be tried. A patient in Denmark failed to respond to evening primrose oil or fish oil, but responded to pentoxifylline. That finding could help About 1988 a medical detailer reported that a general practitioner in a country town (Oamaru) was using pentoxifylline (Trental) to treat his ME patients. But before I could arrange a meeting the doctor was killed in a freak accident at a car rally where he was acting as a marshal As many studies have shown that pentoxifylline improves red cell deformability and reduces blood viscosity, it has the properties to be helpful for ME people but no reports of its use in ME have been located. Despite the lack of placebo-controlled studies, I have had many letters and emails from people who have Continued on page 31) Page 30/34
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